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Physiology
Faculty of Medicine
Diponegoro University
HEMATOLOGY
Removal of wastes
Carbon dioxide, nitrogenous wastes, cellular toxins
Repair of vessels
Protection versus invading microorganisms
Multiple cellular & non-cellular elements
Department of Physiology Diponegoro University Faculty of Medicine
HEMATOLOGY
Hematopoiesis
In humans, occurs in bone marrow exclusively
All cellular elements derived from pluripotent
stem cell (PPSC)
PPSC retains ability to both replicate itself and
differentiate
Types of differentiation determined by the
influence of various cytokines
ERYTHROPOIETIN
A hormone produced in the kidney (probably peritubular cells)
A transmembrane protein; cytokine receptor superfamily
Necessary for erythroid proliferation and differentiation
Its absence results in apoptosis (programmed cell death) of
erythroid committed cells
Binds specifically to Erythropoietin Receptor
Binding leads to dimerization of receptor dimerization
activates tyrosine kinase activity multiple cytoplasmic &
nuclear proteins phosphorylated
Nuclear signal sent to activate production of proteins leading to
proliferation and differentiation
ERYTHROPOIETIN
Regulation of Production
RBC Precursors
Pronormoblast
Basophilic normoblast
Polychromatophilic Normoblast
Orthrochromatophilic Normoblast
Reticulocyte
Mature Red Blood Cell
5-7 days from Pronormoblast to Reticulocyte
Department of Physiology Diponegoro University Faculty of Medicine
RBC Assessment
Number - Generally done by automated counters,
using impedance measures
Size - Large, normal size, or small; all same size
versus variable sizes (anisocytosis). Mean volume
by automated counter
Shape - Normal biconcave disc, versus
spherocytes, versus oddly shaped cells
(poikilocytosis)
Color - Generally an artifact of size of cell
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Normal Values
RBC Parameters
Normal Values
Hematocrit
Females
35-47%
Males
40-52%
Hemoglobin
Females
12.0-16.0 gm/dl
Males
13.5-17.5 gm/dl
MCV
80-100 fl
Reticulocyte Count
0.2-2.0%
RETICULOCYTE
Developmental Aspects
ANEMIA
Causes
Blood loss
Decreased production of red blood cells (Marrow
failure)
Increased destruction of red blood cells
Hemolysis
LEUKOCYTES AND
IMMUNITY
Leukocytes (WBCs)
Granulocytes
Neutrophils
Eosinophils
Basophils
granules stain pink,
blue or purple (Wrights
stain)
larger and usually
shorter-lived than
RBCs
Have lobed nuclei
Are all phagocytic cells
Agranulocytes
lymphocytes and
monocytes:
Lack visible
cytoplasmic granules
Have spherical
(lymphocytes) or
kidney-shaped
(monocytes) nuclei
Agranulocyte
Granulocyte
Granulocytes
Neutrophils
Eosinophils
Basophils
Agranulocytes
Lymphocytes
Monocytes
Monocytes
Macrophages:
Are highly mobile and actively phagocytic
Activate lymphocytes to mount an immune
response
Leukocytes (WBCs)
Neutrophil
Eosinophil
Lymphocyte
Basophil
Monocyte
Production of Leukocytes
Formation of Leukocytes
All leukocytes originate from hemocytoblasts
Hemocytoblasts differentiate into myeloid stem cells
and lymphoid stem cells
Myeloid stem cells become myeloblasts or
monoblasts
Lymphoid stem cells become lymphoblasts
Myeloblasts develop into eosinophils, neutrophils,
and basophils
Monoblasts develop into monocytes
Lymphoblasts develop into lymphocytes
Department of Physiology Diponegoro University Faculty of Medicine
Formation of Leukocytes
Immune response
WBC disorder
Leukopenia
WBC count less than normal
Caused by viral or intracell bacteria infection,
drugs
Leukocytosis
WBC count more than normal
Caused by bacterial infection
Leukemia
WBC malignancy
Department of Physiology Diponegoro University Faculty of Medicine
Leukocytes Disorders
NORMAL
Leukemia
white blood cell cancer
Myelocytic leukemia
involves
myeloblasts
Lymphocytic
leukemia involves
lymphocytes
Acute leukemia primarily affects children
Chronic leukemia - more
prevalent in older people
AML
ALL
CML
www-sdc.med.nagasaki-u.ac.jp/. ../Leukemia-E.html
PLATELETS
AND
HEMOSTASIS
HEMOSTASIS
Platelets
Platelets are fragments of megakaryocytes with a bluestaining outer region and a purple granular center
Platelets are irregularly-shaped, colorless bodies that
are present in blood.
Their sticky surface lets them form clots to stop
bleeding.
Their granules contain serotonin, Ca2+, enzymes, ADP,
and platelet-derived growth factor (PDGF)
Platelets function in the clotting mechanism by forming a
temporary plug that helps seal breaks in blood vessels
Platelets not involved in clotting are kept inactive by NO
and prostaglandin I2
Department of Physiology Diponegoro University Faculty of Medicine
Genesis of Platelets
The stem cell for platelets is the hemocytoblast
The sequential developmental pathway is
hemocytoblast, megakaryoblast,
promegakaryocyte, megakaryocyte, and platelets
Coagulation
Coagulation
Hemostasis Disorders:
Thromboembolytic Conditions
Thrombus a clot that develops and persists in
an unbroken blood vessel
Thrombi can block circulation, resulting in tissue
death
Coronary thrombosis thrombus in blood vessel of
the heart
Blood Typing
Positive reactions indicate agglutination
Humans have 30 varieties of naturally occurring
RBC antigens
The antigens of the ABO and Rh blood groups
cause vigorous transfusion reactions when they
are improperly transfused
Other blood groups (M, N, Dufy, Kell, and
Lewis) are mainly used for legalities
When serum containing anti-A or anti-B
agglutinins is added to blood, agglutination will
occur between the agglutinin and the
corresponding agglutinogens
Department of Physiology Diponegoro University Faculty of Medicine
Table 17.4
Department of Physiology Diponegoro University Faculty of Medicine
Blood Typing
RBC agglutinogens
Serum Reaction
Anti-A
Anti-B
AB
A and B
None
Rh Blood Groups
Blood Types
Antigens
A, B, AB, O
Universal donors
Rh factor
Whole blood transfusions are used:
When blood loss is substantial
In treating thrombocytopenia
Packed red cells (cells with plasma removed)
are used to treat anemia
Transfusion Reactions
Hemolytic Reactions
Signs and Symptoms
Facial flushing, hyperventilation,
tachycardia, hives, chest pain, wheezing,
fever, chills, and cyanosis.
Treatment
Stop transfusion, change all IV tubing, and
initiate IV therapy with normal saline or
lactated Ringers.Consider furosemide,
dopamine, and diphenhydramine.
Febrile Nonhemolytic Reactions
Signs and Symptoms
Headache, fever, and chills.
Department of Physiology Diponegoro University Faculty of Medicine
Transfusion Reactions
A GLANCE OF IMMUNOLOGY:
INNATE AND ADAPTIVE
IMMUNITY
(hanya sebagai tambahan materi)
Abbas &
Lichtman,2005
Department of Physiology Diponegoro University Faculty of Medicine
Mechanism of Phagocytosis
Figure 21.1a, b
Antimicrobial Proteins
Events in Inflammation
Figure 21.2
Department of Physiology Diponegoro University Faculty of Medicine
Antigens
The ultimate targets of all immune responses are
mostly large, complex molecules not normally
found in the body (nonself)
Antigens are substances that can mobilize the
immune system and provoke an immune response
Only certain parts of an entire antigen are
immunogenic. Antibodies and activated
lymphocytes bind to these antigenic determinants
Antibodies
Also called immunoglobulins
Constitute the gamma
globulin portion of blood
proteins
Are soluble proteins
secreted by activated B
cells and plasma cells in
response to an antigen
Are capable of binding
specifically with that
antigen
There are five classes of
antibodies: IgD, IgM, IgG,
IgA, and IgE
Department of Physiology Diponegoro University Faculty of Medicine
Figure 21.13
Figure 21.10
Figure 21.11
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Figure 21.14
Department of Physiology Diponegoro University Faculty of Medicine
MHC Proteins
Both types of MHC proteins are important to T
cell activation
Class I MHC proteins:
Always recognized by CD8 T cells
Display peptides from endogenous antigens
Class II MHC proteins
Found only on mature B cells, some T cells,
and antigen-presenting cells
Antigen recognition:
Provides the key for the immune system to
recognize the presence of intracellular
microorganisms
Department of Physiology Diponegoro University Faculty of Medicine
Antigen Recognition
Figure 21.16
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Cytokines
Mediators involved in cellular immunity, including hormone-like
glycoproteins released by activated T cells and macrophages
Some are co-stimulators of T cells and T cell proliferation
Interleukin 1 (IL-1) released by macrophages co-stimulates bound T
cells to:
Release interleukin 2 (IL-2)
Synthesize more IL-2 receptors
IL-2 is a key growth factor, which sets up a positive feedback cycle that
encourages activated T cells to divide
It is used therapeutically to enhance the bodys defenses against
cancer
Other cytokines amplify and regulate immune and nonspecific
responses
Examples include:
Perforin and lymphotoxin cell toxins
Gamma interferon enhances the killing power of macrophages
Inflammatory factors
Department of Physiology Diponegoro University Faculty of Medicine
Figure 21.17a
Department of Physiology Diponegoro University Faculty of Medicine
Mechanisms of Tc Action
Figure 21.18a, b
Importance of
Humoral Response
Soluble antibodies
The simplest
ammunition of
the immune
response
Interact in
extracellular
environments
such as body
secretions, tissue
fluid, blood, and
lymph
Importance of
Cellular Response
T cells recognize and respond
only to processed fragments of
antigen displayed on the
surface of body cells
T cells are best suited for cellto-cell interactions, and target:
Cells infected with viruses,
bacteria, or intracellular
parasites
Abnormal or cancerous cells
Cells of infused or
transplanted foreign tissue
Figure 21.19
Department of Physiology Diponegoro University Faculty of Medicine